Qian JunQing, Jiang Zhaorong, Li Min, Heaphy Paige, Liu Yi-Hsin, Shackleford Gregory M
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Genomics. 2003 Jan;81(1):34-46. doi: 10.1016/s0888-7543(02)00012-5.
The members of the Wnt family of secreted factors have oncogenic potential and important roles as developmental regulators. We report an analysis of mouse Wnt9b (also called Wnt15 and Wnt14b), including its cDNA sequence, chromosomal mapping, epithelial cell transforming activity, adult and embryonic tissue expression patterns, and evolution. We also deduced the full-length amino acid sequence of its close relative, Wnt9a (also called Wnt14), from unannotated genomic DNA sequences in GenBank. Full-length comparisons among Wnt amino acid sequences provide evidence that Wnt9b and Wnt9a are close paralogs of each other and are orthologs of Wnt9 genes from shark and hagfish. Mapping Wnt9b to The Jackson Laboratory BSS interspecific backcross panel places it at 63.0 cM on chromosome 11. Sequence comparisons of two pairs of linked Wnt genes (the Wnt9a-Wnt3a pair and the Wnt9b-Wnt3 pair) suggest that they arose from the relatively recent duplication of a single ancestral Wnt gene pair, confirming the close paralogous relationship of Wnt9a and Wnt9b. Wnt9b expression is primarily restricted to the kidney in the adult mouse, with lower levels detected in the preputial gland, liver, and mammary gland. Testing of staged whole mouse embryos from 9.5 to 17.5 days of gestation showed expression at all stages with a peak at day 10.5. In situ hybridization analysis showed expression in most but not all tissues of the 16.5-day embryo. No significant elevation of Wnt9b expression was detected in 29 mouse mammary tumor virus-induced tumors. Overexpression of Wnt9b in C57MG mammary epithelial cells caused small transformed foci in cell monolayers and a moderate morphological transformation in pooled colonies compared with Wnt1.
分泌因子Wnt家族的成员具有致癌潜力，并且作为发育调节因子发挥着重要作用。我们报告了对小鼠Wnt9b（也称为Wnt15和Wnt14b）的分析，包括其cDNA序列、染色体定位、上皮细胞转化活性、成年和胚胎组织表达模式以及进化情况。我们还从GenBank中未注释的基因组DNA序列推导了其近亲Wnt9a（也称为Wnt14）的全长氨基酸序列。Wnt氨基酸序列的全长比较提供了证据，表明Wnt9b和Wnt9a是彼此紧密的旁系同源物，并且是鲨鱼和盲鳗Wnt9基因的直系同源物。将Wnt9b定位到杰克逊实验室BSS种间回交面板上，它位于11号染色体上63.0 cM处。两对连锁Wnt基因（Wnt9a-Wnt3a对和Wnt9b-Wnt3对）的序列比较表明，它们起源于单个祖先Wnt基因对的相对近期复制，证实了Wnt9a和Wnt9b紧密的旁系同源关系。Wnt9b表达在成年小鼠中主要局限于肾脏，在包皮腺、肝脏和乳腺中检测到较低水平。对妊娠9.5至17.5天的分期全小鼠胚胎进行检测，结果显示在所有阶段均有表达，在第10.5天达到峰值。原位杂交分析显示，在16.5天胚胎的大多数但并非所有组织中均有表达。在29个小鼠乳腺肿瘤病毒诱导的肿瘤中未检测到Wnt9b表达的显著升高。与Wnt1相比，Wnt9b在C57MG乳腺上皮细胞中的过表达在细胞单层中导致小的转化灶，在汇集菌落中导致中等程度的形态转化。
